Overcoming infection is a struggle that all eukaryotic organisms have to face to survive and evolve among the ubiquitously present microorganisms. Studying host-microbe interactions is of fundamental importance to the development of medicine, agriculture and many other human affairs, including the fight against the threat of bio-terrorism. The long-term goal of this project is to understand the molecular mechanisms by which plants defend themselves against infection. The Arabidopsis NPR1 protein is a master regulator of multiple defense pathways. It is required for the salicylic acid (SA)-mediated systemic acquired resistance (SAR). Mutations in NPR1 abolish SA-induced gene expression and SAR. Upon induction, NPR1 is nuclear localized to activate gene expression. However, the mechanism of this key regulatory step is unknown. Besides SAR, NPR1 is also involved in SA-mediated cross-talk inhibition of a defense pathway induced by jasmonic acid. Understanding the dual role of NPR1 in SAR and JA-signaling will be essential for understanding the control mechanisms and interactions between these pathways. Moreover, identification of target genes of NPR1 in each response will lead to new insights into the molecular basis for these defense responses. Therefore, the two specific aims of this project are: (1) Determine the regulatory mechanisms that control NPR1 activity. Through this specific aim, it will be determined how elevation of cellular SA levels leads to nuclear translocation and activation of the NPR1 protein. The effects of different chemical modifications such as disulfide bond formation and protein phosphorylation on NPR1 protein activity will be examined. (2) Elucidate NPR1 functions in different defense pathways. This specific aim will focus on understanding how NPR1, in response to SA, plays a dual role as a positive regulator of SAR and a negative regulator of JA-mediated defense pathway and what genes NPR1 regulates in these two defense pathways. Better understanding of plant immunity will have both theoretical and practical significance. Comparing immune responses in plants and animals may lead to discovery of common mechanisms governing host-microbe interactions. Using plants' innate immunity to control crop disease may lead to replacement of pesticides, many of which cause pollution of the environment and are harmful to human health.